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Muscling toward a longer life: Genetic aging pathway identified in flies
Date:10/17/2011

espan is more significant."

Fruit flies normally live about fifty days in Sanyal's laboratory, depending on temperature and conditions. Some strains of fly that overproduce p38 MAP kinase live on average about 75 days, 50 percent longer than regular flies (green line in graph below). For this effect, it is sufficient that p38 is overproduced in muscles only.

Vrailas-Mortimer showed that a protein that protects cells against oxidative stress that is found in mitochondria, superoxide dismutase (MnSOD), is responsible for at least some of p38 MAP kinase's effects on aging. A third gene called MEF2 is also involved, in between p38 MAP kinase and MnSOD. Mitochondria are cells' miniature power plants and are more abundant in muscle.

Giving flies more MnSOD can restore a more normal lifespan to the p38 mutants. Other types of antioxidant enzymes don't rescue lifespan in flies with p38 mutations, the researchers found.

P38, MEF2 and MnSOD's action in muscles distinguishes them from a well-studied genetic circuit regulating aging in the worm C. elegans as well as flies and mice, which appears to work through insulin-like hormone responses in the brain and other tissues. Caloric restriction (consistently eating less), an established way of lengthening lifespan, acts through this insulin-like signaling pathway.

"It may be that oxidative stress is especially important in flies' muscles because flies' energy use is so high," Sanyal says. "The role oxidative stress plays in aging is well-known, so its involvement here was not a surprise. I think what's new here is finding a genetic pathway regulating aging that is specific to muscles and separate from insulin signaling."

Sanyal says he and his team plan to examine what kinds of dietary antioxidants can extend lifespan in flies without p38. They also plan to probe how caloric restriction interacts with p38 deficiency.


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Contact: Holly Korschun
hkorsch@emory.edu
404-727-3990
Emory University
Source:Eurekalert  

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